Identification of the UBP1 Locus as a Critical Blood Pressure Determinant Using a Combination of Mouse and Human Genetics

Hypertension is a major health problem of largely unknown genetic origins. To identify new genes responsible for hypertension, genetic analysis of recombinant inbred strains of mice followed by human association studies might prove powerful and was exploited in our current study. Using a set of 27 recombinant BXD strains of mice we identified a quantitative trait locus (QTL) for blood pressure (BP) on distal chromosome 9. The association analysis of markers encompassing the syntenic region on human chromosome 3 gave in an additive genetic model the strongest association for rs17030583 C/T and rs2291897 G/A, located within the UBP1 locus, with systolic and diastolic BP (rs17030583: 1.3±0.4 mmHg p<0.001, 0.8±0.3 mmHg p = 0.006, respectively and rs2291897: 1.5±0.4 mmHg p<0.001, 0.8±0.3 mmHg p = 0.003, respectively) in three separate studies. Our study, which underscores the marked complementarities of mouse and human genetic approaches, identifies the UBP1 locus as a critical blood pressure determinant. UBP1 plays a role in cholesterol and steroid metabolism via the transcriptional activation of CYP11A, the rate-limiting enzyme in pregnenolone and aldosterone biosynthesis. We suggest that UBP1 and its functional partners are components of a network controlling blood pressure

Correction to:Yoghurt consumption is associated with changes in the composition of the human gut microbiome and metabolome (BMC Microbiology, (2022), 22, 1, (39), 10.1186/s12866-021-02364-2)

Following the publication of the original paper [1], there’s an error on the first name of one of the authors. Mureil Derrien should be Muriel Derrien. Correct name is shown in the author group section above. The original article has been corrected

Pparγ2 Is a Key Driver of Longevity in the Mouse

Aging involves a progressive physiological remodeling that is controlled by both genetic and environmental factors. Many of these factors impact also on white adipose tissue (WAT), which has been shown to be a determinant of lifespan. Interrogating a transcriptional network for predicted causal regulatory interactions in a collection of mouse WAT from F2 crosses with a seed set of 60 known longevity genes, we identified a novel transcriptional subnetwork of 742 genes which represent thus-far-unknown longevity genes. Within this subnetwork, one gene was Pparg (Nr1c3), an adipose-enriched nuclear receptor previously not associated with longevity. In silico, both the PPAR signaling pathway and the transcriptional signature of Pparγ agonist rosiglitazone overlapped with the longevity subnetwork, while in vivo, lowered expression of Pparg reduced lifespan in both the lipodystrophic Pparg1/2-hypomorphic and the Pparg2-deficient mice. These results establish Pparγ2 as one of the determinants of longevity and suggest that lifespan may be rather determined by a purposeful genetic program than a random process

PPARγ, an X-ceptor for Xs

International audienceEvidence from both human genetic studies and characterization of peroxisome proliferator-activated receptor gamma (PPARgamma) knockout mice suggested that the prime function of PPARgamma is fat formation and that its role in insulin sensitization might be secondary to this function. The thrifty function of PPARgamma was most likely evolutionary beneficial, but might in "times of plenty" contribute to the pathogenesis of disorders, such as obesity, insulin resistance, type 2 diabetes, and hyperlipidemia, often commonly referred to as "syndrome X". This role of PPARgamma in these diseases also questions the eventual therapeutic benefits of pure PPARgamma activation, which is associated with an increase in adipose tissue mass. We characterized a new chemical class of PPARgamma agonists, that is, FMOC-l-leucine (FLL). FLL induces a different conformation of PPARgamma relative to classical PPARgamma ligands. Mass spectrometry indicates that two molecules of FLL bind to a single PPARgamma molecule, making its mode of receptor interaction distinctive. FLL recruits a different set of coactivators and activates PPARgamma with a lower potency, but a similar maximal efficacy, relative to known PPARgamma ligands. In contrast, FLL is a more effective insulin sensitizer than current PPARgamma agonists, an effect potentially linked to its weak adipogenic activity. These data make a strong point for potential therapeutic benefits of PPARgamma modulation rather than activation

Upstream binding protein 1 polymorphisms and their use for prognosing or diagnosing arterial blood pressure

The present invention is directed to methods for diagnosis and prognosis using polymorphic variants of Ubp 1 s and related probes and kits

Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials

International audienceOBJECTIVE: To systematically review the effect of oral intake of bacterial probiotics on 15 variables related to obesity, diabetes and non-alcoholic fatty liver disease.DESIGN: Systematic review and meta-analysis.DATA SOURCES: Medline, EMBASE and COCHRANE from 1990 to June 2018.ELIGIBILITY CRITERIA: Randomised controlled trials (≥14 days) excluding hypercholesterolaemia, alcoholic liver disease, polycystic ovary syndrome and children <3 years.RESULTS: One hundred and five articles met inclusion criteria, representing 6826 subjects. In overweight but not obese subjects, probiotics induced improvements in: body weight (k=25 trials, d=-0.94 kg mean difference, 95% CI -1.17 to -0.70, I²=0.0%), body mass index (k=32, d=-0.55 kg/m², 95% CI -0.86 to -0.23, I²=91.9%), waist circumference (k=13, d=-1.31 cm, 95% CI -1.79 to -0.83, I²=14.5%), body fat mass (k=11, d=-0.96 kg, 95% CI -1.21 to -0.71, I²=0.0%) and visceral adipose tissue mass (k=5, d=-6.30 cm², 95% CI -9.05 to -3.56, I²=0.0%). In type 2 diabetics, probiotics reduced fasting glucose (k=19, d=-0.66 mmol/L, 95% CI -1.00 to -0.31, I²=27.7%), glycated haemoglobin (k=13, d=-0.28 pp, 95% CI -0.46 to -0.11, I²=54.1%), insulin (k=13, d=-1.66 mU/L, 95% CI -2.70 to -0.61, I²=37.8%) and homeostatic model of insulin resistance (k=10, d=-1.05 pp, 95% CI -1.48 to -0.61, I²=18.2%). In subjects with fatty liver diseases, probiotics reduced alanine (k=12, d=-10.2 U/L, 95% CI -14.3 to -6.0, I²=93.50%) and aspartate aminotransferases (k=10, d=-9.9 U/L, 95% CI -14.1 to -5.8, I²=96.1%). These improvements were mostly observed with bifidobacteria (Bifidobacterium breve, B. longum), Streptococcus salivarius subsp. thermophilus and lactobacilli (Lactobacillus acidophilus, L. casei, L. delbrueckii) containing mixtures and influenced by trials conducted in one country.CONCLUSIONS: The intake of probiotics resulted in minor but consistent improvements in several metabolic risk factors in subjects with metabolic diseases

Isolation and characterisation of X chromosome-derived DNA sequences from a dioecious plant Melandrium album

Bůžek, Jiří ; Koutníková, Hana ; Houben, Andreas ; Říha, Karel ; Janousśek, Bohuslav ; Široký, Jiří ; Grant, Sarah ; Vyskot, Bori

Adipose Tissue Expression of the Lipid Droplet–Associating Proteins S3-12 and Perilipin Is Controlled by Peroxisome Proliferator–Activated Receptor-γ

International audienceIn a systematic search for peroxisome proliferator–activated receptor-γ (PPAR-γ) target genes, we identified S3-12 and perilipin as novel direct PPAR-γ target genes. Together with adipophilin and tail-interacting protein of 47 kDa, these genes are lipid droplet–associating proteins with distinct expression pattern but overlapping expression in adipose tissue. The expression of S3-12 and perilipin is tightly correlated to the expression and activation of PPAR-γ in adipocytes, and promoter characterization revealed that the S3-12 and the perilipin promoters contain three and one evolutionarily conserved PPAR response elements, respectively. We furthermore demonstrate that the expression of S3-12 and perilipin is reduced in obese compared with lean Zucker rats, whereas the expression of adipophilin is increased. Others have shown that perilipin is an essential factor in the hormonal regulation of lipolysis of stored triglycerides within adipose tissue. The direct regulation of perilipin and S3-12 by PPAR-γ therefore is likely to be an important mediator of the in vivo effects of prolonged treatment with PPAR-γ activators: insulin sensitization, fatty acid trapping in adipose tissue, reduced basal adipose lipolysis, and weight gain

The Pro12Ala PPARgamma2 variant determines metabolism at the gene-environment interface.

International audienceThe metabolic impact of the common peroxisome proliferator-activated receptor gamma isoform 2 (PPARgamma2) variant Pro12Ala in human populations has been widely debated. We demonstrate, using a Pro12Ala knockin model, that on chow diet, Ala/Ala mice are leaner, have improved insulin sensitivity and plasma lipid profiles, and have longer lifespans. Gene-environment interactions played a key role as high-fat feeding eliminated the beneficial effects of the Pro12Ala variant on adiposity, plasma lipids, and insulin sensitivity. The underlying molecular mechanisms involve changes in cofactor interaction and adiponectin signaling. Altogether, our results establish the Pro12Ala variant of Ppargamma2 as an important modulator in metabolic control that strongly depends on the metabolic context